The Impact of Genetic Variants for Different Physiological Characterization of Type 2 Diabetes Loci on Gestational Insulin Signaling in Nondiabetic Pregnant Chinese Women

Reprod Sci. 2015 Nov;22(11):1421-8. doi: 10.1177/1933719115580995. Epub 2015 Apr 14.

Abstract

We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m(2)) and gave them oral glucose tolerance tests. Matsuda index of insulin sensitivity, homeostatic model assessment of insulin resistance, indices of insulin disposition, early-phase insulin release, fasting state, and 0 to 120 minute's proinsulin to insulin conversion were used to dissect insulin physiological characterization. Several variants related to β-cell function were genotyped. The genetic impacts were analyzed using logistic regression under an additive model. By adjusting for maternal age, BMI, and the related interactions, the genetic variants in ABCC8, CDKAL1, CDKN2A, HNF1B, KCNJ11, and MTNR1B were detected to impact gestational insulin signaling through heterogeneous mechanisms; however, compared with that in nonpregnant metabolism, the genetic effects seem to be eminently and heavily influenced by maternal age and BMI, indicating possible particular mechanisms underlying gestational metabolism and diabetic pathogenesis.

Keywords: genetic variants; gestational diabetes; gestational insulin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Blood Glucose / genetics
  • Blood Glucose / metabolism
  • Body Mass Index
  • China
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / ethnology
  • Diabetes, Gestational / genetics*
  • Female
  • Gene-Environment Interaction*
  • Genetic Loci*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance / ethnology
  • Insulin Resistance / genetics
  • Insulin-Secreting Cells / metabolism*
  • Logistic Models
  • Maternal Age
  • Phenotype
  • Pregnancy
  • Signal Transduction*
  • Young Adult

Substances

  • Blood Glucose
  • Genetic Markers
  • Insulin